Two different aspects of regulation of collagen synthesis are being studied. The objective of one project is to determine the mechanism by which vitamin C (ascorbic acid) controls connective tissue metabolism. Previously we showed that decreased collagen synthesis in parietal bone of scorbutic guinea pigs was directly related to the extent of weight loss during the third and fourth week of scurvy, rather than to defective proline hydroxylation. Our current studies show that collagen synthesis in cartilage is similarly affected by scurvy and tha synthesis of another major components of cartilage extracellular matrix, proteoglycan, is also decreased. Both effects as directly correlated with weight loss and synthesis of collagen and proteoglycans appears to be coorditely regulated. These, and other results, suggest that ascorbate deficiency indirectly produces these effects by inducing anorexia, which leads to a chronic fasting state. Acute fasting for 96 hr with ascorbate supplementation causes a similar coordinate reduction in collagen and proteoglycan production. Decreased collagen production in both bone and cartilage of acutely fasted animals is not due to an increase in degradation but to decreased synthesis caused by a reduction in the levels of procollagen mRNA. In a second study, we have found that in a nitroquinoline oxide transformant of BALB 3T3 (NQT-3T3), there is almost complete supression of synthesis of type I procollagen, the major product of the parent 3T3 cells. In addition, synthesis of two previously undescribed types of collagen is induced. Both of these molecules appear to have a procollagen type of structure. Each is composed of single subunits with a pepsin-resistant helical region having a typical repeating tripeptide sequence susceptible to bacterial collagenase, plus pepsin-sensitive noncollagenous regions.